Endothelial cells contribute to vascular integrity through maintenance of an anatomic barrier and release of substances which inhibit thrombosis. Loss of endothelial cell function or change in structure may play an instrumental role in the genesis of thrombosis, atherosclerosis, vasculitis, and hemorrhagic disorders. In this project, properties of the endothelium will be investigated: 1) following sublethal injury by immunoglobulin with endothelial cell specificity or to immune aggregates either alone or in the presence of complement and 2) during replication in culture - a system to study rapidly proliferating endothelial cells. Cultured human and bovine vascular endothelial cells and an ex vivo model using vascular strips will be studied. Specific properties of the endothelium will be examined under both injurious and replicating conditions. These properties include: 1) Prostacyclin (PGI2) production and release 2) Prostaglandin E2 production and release 3) Angiotensin converting enzyme (ACE) activity 4) Plasminogen Activator (PA) activity 5) Protein C Cofactor. Prostaglandins I2 and E2 play important roles in vascular homeostasis and inflammation. ACE is a regulator of vascular tone. PA is important in cell growth, cell spreading, wound healing, and cell-cell interactions. Protein C Cofactor, through thrombin activation of Protein C inhibits factors Va and VIIIa and plays a role in promoting fibrinolysis. The effects of sublethal injury on confluent and nonconfluent cell monolayers will be studied using flow cytometry to obtain high DNA content populations of cells which will be used to address the question of whether endothelial cell properties are modified during periods of rapid growth. These studies will clarify alterations in the anatomic and physiologic function of endothelial cells in response to sublethal injury and during times of rapid cell division.